Alcohol consumption and cardiovascular disease (CVD) in HIV

ABSTRACT
Objectives: Cardiovascular disease (CVD) is a major concern in HIV-infected patients as antiretroviral therapy (ART) and patients’ lifestyle can potentially increase CVD risk. Clinical and socio-behavioral data from the French ANRS CO8 APROCO-COPILOTE cohort were used to investigate the relationship
between alcohol use and CVD in HIV-infected individuals receiving ART.
Methods: The APROCO-COPILOTE cohort was set up in 1996 with the aim of studying the course of the clinical, immunological and virological progression after ART initiation. Patient-reported outcomes (adherence, quality of life, symptoms) and other information were collected at baseline, months 1, 4,
12 and every 8 months subsequently by self-administered questionnaires. Alcohol use was assessed using 2 questions that allowed determination of mean number of alcohol units (AU) consumed per day at each follow-up assessment. Metabolic data were available only for a subset of patients. A Cox
model was applied to estimate the association between self-reported daily alcohol consumption (at baseline and during follow-up) and the first occurrence of CVD after adjustment for known correlates and potential confounders on the whole dataset and also for metabolic correlates using the
restricted dataset.
Results: Over the whole follow-up of the cohort (n=1154), 85 CVD events were observed (incidence rate [95% CI]=1.3 [1.0-1.6] per 100 PY), including coronary artery disease/myocardial infarction (n=30), phlebitis/pulmonary embolism (n=22), cardiomyopathy/congestive heart failure (n=9), stroke (n=7),
peripheral vascular disease (n=7), other events (cardiac dysrhythmia, cerebral haemorrhage, aortic aneurysm, cardiovascular surgery). In the restricted database with metabolic data (n=675), after adjustment for age (HR [95% CI]: 1.08 [1.05-1.11]), smoking more than 20 cigarettes/day (4.12 [2.22-7.64]),
CD4>200 (0.48 [0.22-1.04]), undetectable viral load (0.47 [0.27-0.81]) and hyperlipidemia (2.54 [1.33-4.85]), individuals with moderate alcohol consumption(<=3 AU/day vs. abstainers) were at lower risk of CVD (0.37 [0.21-0.64], p<0.001) while those drinking more than 3 AU/day were not significantly different than abstainers (0.53 [0.17-1.65]). These results about moderate alcohol use remained valid (0.58 [0.36-0.95]) even if computed on the complete database without adjustment for hyperlipidemia.
Conclusions: Alcohol consumption has no negative impact on CVD risk, relative to abstainers’ category. Like in the general population, moderate alcohol consumption seems to play a protective role in the onset of CVD, after adjustment for known risk factors. Due to the limited number and heterogeneity of CVD events, a multi-cohort analysis may be needed to better explore the impact of alcohol consumption on specific CVD in ART-treated individuals.
Alcohol consumption and cardiovascular disease (CVD)
in HIV-infected patients receiving antiretroviral treatment (ART)
Results from the ANRS CO8 APROCO-COPILOTE cohort
AUT HORS
Results
Maria Patrizia Carrieri1,2, Camelia Protopopescu1,2,
Geneviève Chêne3, Dominique Salmon-Ceron4, Bruno Spire1,2,
Bruno Marchou5, Frédéric Bastides6, François Raffi7,
Catherine Leport8 and the APROCO-COPILOTE ANRS CO8 study group
1 INSERM U912 "Economic & Social Sciences, Health Systems & Societies", Marseilles, France
2 IRD, Aix-Marseille Université, Southeastern Health Regional Observatory (ORS-PACA), Marseilles, France
3 INSERM, U897, Bordeaux, France;
4 CHU Cochin, Paris, France;
5 Hôpital de Purpan, Toulouse, France;
6 CHRU Tours, France;
7 CHRU Hôtel Dieu, Nantes, France;
8 LRPI, Université Paris Diderot-Paris 7, Paris, France
Background
Cardiovascular disease (CVD) is a major concern in HIV-infected
patients as antiretroviral therapy (ART) and patients’ lifestyle
can potentially increase CVD risk
Several observational studies have found that heavy alcohol
consumption was associated with higher CVD risk in people
with HIV
In contrast, recent studies suggest that moderate drinking is
inversely associated with the mortality due to CVD (Mukamal et
al, J Am Coll Cardiol. 2010)
Objective
To investigate the relationship between self-reported alcohol
consumption and the first occurrence of a CVD event, after
adjustment for known risk factors, among ART-treated patients
followed-up in the French APROCO-COPILOTE cohort
Patients and Methods
The French APROCO-COPILOTE cohort (ANRS CO8)
Prospective observational national multicenter study
1281 HIV-1 infected adults started on their first protease
inhibitor-containing therapy in 1997-1999
Data collection
Standardized clinical and biological data collected at
enrollment and every 4 months thereafter: CD4+ cell count,
viral load, CDC clinical stage, HIV transmission group,
antiretroviral naivety at enrollment, HCV co-infection
Self-administered questionnaires collecting socio-demographic
and psychosocial data at M0, M12, M28, and every 8 months
thereafter: age, gender, education, employment, alcohol and
tobacco consumption, among others
Metabolic disorders data collected at enrollment (available
only on a subset of the participants in the cohort): height and
weight, diabetes, hyperlipidemia, personal history of coronary
heart disease (CHD) and hypertension, family history of CHD
Period of follow-up: M0-M132 (11 years)
Two analyses
First study population: all patients with non missing
self-reported alcohol data at baseline (n=1154)
Second study population: the subset of patients with available
metabolic data (n=675)
Statistical analysis
Cox proportional hazard models
Backward selection of explanatory variables in the final
multivariate model
Two outcomes
First, major CVD events were selected for the analysis
(n=46 events for all selected patients):
- myocardial infarction (MI), stroke and congestive heart failure
Second, all CVD events documented in medical records were
considered as outcome
(n=85 events for all selected patients):
- major CVD events (as above), plus peripheral vascular
disease, cardiac dysrhythmia, phlebitis and pulmonary
embolism
Acknowledgements
Participating patients & hospital teams
We warmly thank the patients who participated in the cohort
The APROCO-COPILOTE (ANRS CO8) Study Group
Scientific Committee: Steering Committee:
Principal investigators: C. Leport, F. Raffi
Methodology: G. Chêne, R. Salamon
Social sciences: J-P. Moatti, J. Pierret, B. Spire
Virology: F. Brun-Vézinet, H. Fleury, B. Masquelier
Pharmacology: G. Peytavin, R. Garraffo
Other members: D. Costagliola, P. Dellamonica, C. Katlama, L. Meyer, D. Salmon, A. Sobel.
Events Validation Committee: L. Cuzin, M. Dupon, X. Duval, V. Le Moing, B. Marchou, T. May, P. Morlat, C. Rabaud, A.
Waldner-Combernoux
Project coordination: F. Collin-Filleul
Clinical Research Group: V. Le Moing, C. Lewden
Clinical Centres (investigators): Amiens (Pr JL. Schmit), Angers (Dr JM. Chennebault), Belfort (Dr JP. Faller), Besançon (Pr JL.
Dupond, Dr JM. Estavoyer, Dr Drobachef), Bobigny (Pr O. Bouchaud), Bordeaux (Pr M. Dupon, Pr Longy-Boursier, Pr P. Morlat, Pr
JM. Ragnaud), Bourg-en-Bresse (Dr P. Granier), Brest (Pr M. Garré), Caen (Pr R. Verdon), Compiègne (Dr D. Merrien), Corbeil
Essonnes (Dr A. Devidas), Créteil (Pr A. Sobel), Dijon (Pr H. Portier), Garches (Pr C. Perronne), Lagny (Dr P. Lagarde), Libourne (Dr
J. Ceccaldi), Lyon (Pr D. Peyramond), Meaux (Dr C. Allard), Montpellier (Pr J. Reynes), Nancy (Pr T. May), Nantes (Pr F. Raffi), Nice
(Pr JG Fuzibet, Pr P. Dellamonica), Orléans (Dr P. Arsac), Paris (Pr E. Bouvet, Pr F. Bricaire, Pr P. Bergmann, Pr J. Cabane, Dr J.
Monsonego, Pr P.M. Girard, Pr L. Guillevin, Pr S. Herson, Pr C. Leport, Pr MC. Meyohas, Pr J.M. Molina, Pr G. Pialoux, Pr D. Salmon),
Poitiers (Pr B. Becq-Giraudon), Reims (Pr R. Jaussaud), Rennes (Pr C. Michelet), Saint-Etienne (Pr F. Lucht), Saint-Mandé (Pr T.
Debord), Strasbourg (Pr JM Lang), Toulon (Dr JP. De Jaureguiberry), Toulouse (Pr B. Marchou), Tours (Pr JM. Besnier).
Data monitoring and statistical analysis: C. Alfaro, S. Boucherit, AD Bouhnik, C. Brunet-François, M.P. Carrieri, M. Courcoul, F.
Couturier, J.L. Ecobichon, M. François, V. Guiyedi, L. Iordache. P. Kurkdji, JP Legrand, S. Martiren, E. Pereira, M. Préau, C.
Protopopescu, C. Roy, J. Surzyn, A. Taieb, V. Villes, H. Zouari.
Promotion: Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS, Action Coordonnée n°7).
Other support: Collège des Universitaires de Maladies Infectieuses et Tropicales (CMIT ex APPIT), Sidaction Ensemble contre le
Sida and associated pharmaceutical companies: Abbott, Boehringer-Ingelheim, Bristol-Myers Squibb, Glaxo- SmithKline and
Roche
Sponsoring
Statistical analysis
The median [IQR] duration of follow-up for the study patients is
5.9 [1.8-9.4] years
9401 person-visits are selected for the analysis
Description of CVD events
Major CVD events: MI (n=30), stroke (n=7) and congestive heart
failure (n=9)
Other CVD events: phlebitis/pulmonary embolism (n=22),
peripheral vascular disease (n=7), cardiac dysrhythmia (n=6),
cerebral hemorrhage, aortic aneurysm, cardiovascular surgery
Incidence rate [95% CI] of all CVD events:
1.3 [1.0-1.6] per 100 person-years
Incidence rate [95% CI] for major CVD events:
0.71 [0.53-0.94] per 100 person-years
Characteristics for the study population (n=1154)
Factors associated with all CVD and major CVD events (univariate analyses)
% of patients
All CVD events
Major CVD events
or mean (SD) HR
p-value
HR
p-value
Socio-economic and psychosocial characteristics
Female gender
22.1
NS
0.38
0.068
1.07
<10-3
Age at inclusion° - years
37.7 (9.5)
1.08
<10-3
High-school education°
31.3
0.63
0.063
0.57
0.113
2.85
0.001
Smoking>20 cig/day*
16.4
2.65
<10-3
Alcohol consumption*
- abstainers (ref)
18.8
1
- <=3 AU/day
75.3
0.06
0.018
0.49
0.028
- >3 AU/day
5.9
1.06
0.906
1.14
0.838
Clinical characteristics
HIV transmission category°
- homosexual
40.6
NS
NS
- IDU
17.8
- other (ref)
41.6
CDC clinical stage A°
51.2
0.58
0.023
0.48
0.031
HCV infection°
22.4
1.36
0.212
NS
Antiretroviral naivety°
44.4
NS
NS
CD4+ cell count>=200 cells/mm3°
65.3
0.52
0.039
0.43
0.040
Undetectable viral load*
7.7
0.68
0.085
NS
SD=standard deviation; HR=hazard ratio; NS=p>0.25; ° Fixed variable (measured at M0 or M1)
* Time-varying variable (the last available value before each visit)
Metabolic data for the restricted population (n=675)
Factors associated with all CVD and major CVD events (univariate analyses)
% of patients
or mean (SD)
Metabolic data characteristics
BMI categories°
- underweight: <18.5
- normal weight: 18.5–24.9
- overweight: 25–29.9
- obesity: >30
Diabetes°
Hyperlipidemia°
Personal history of CHD°
Family history of CHD°
Personal history of hypertension°
5.8
72.7
17.0
2.8
1.8
11.3
1.2
28.0
6.1
All CVD events
HR
p-value
1.96
6.06
1.41
2.06
Major CVD events
HR
p-value
NS
NS
0.032
0.002
0.202
0.072
0.055
<10-3
0.010
0.008
2.17
11.9
2.42
3.32
SD=standard deviation; HR=hazard ratio; NS=p>0.25
° Fixed variable (measured at M0 or M1)
Factors independently associated with all CVD and major CVD events
(multivariate analyses, all patients: n=1154)
All CVD events
Major CVD events
HR
p-value
HR
p-value
Alcohol consumption*
- abstainers (ref)
1
1
- <=3 AU/day
0.58 [0.36-0.95] 0.029 0.44 [0.23-0.84] 0.013
- >3 AU/day
0.57 [0.21-1.54]
0.265 0.54 [0.15-1.95] 0.345
Female gender
0.39 [0.14-1.13] 0.083
Age at inclusion° - years
1.09 [1.07-1.11]
<10-3 1.09 [1.06-1.12] <10-3
Smoking>20 cig/day*
4.16 [2.49-6.95]
<10-3 4.09 [2.03-8.25] <10-3
CD4+ cell count>=200 cells/mm3* 0.53 [0.29-1.00]
0.051 0.43 [0.19-0.97] 0.042
Undetectable viral load*
0.62 [0.39-0.97]
0.035
SD=standard deviation; AHR=adjusted hazard ratio ; CI=confidence interval
° Fixed variable (measured at M0 or M1)
Time-varying variable (the last available value before each visit)
Factors independently associated with all CVD and major CVD events
(multivariate analyses, patients with metabolic data: n=675)
All CVD events
Major CVD events
HR
p-value
HR
p-value
Alcohol consumption*
- abstainers (ref)
1
1
- <=3 AU/day
0.37 [0.21-0.64]
<10-3 0.28 [0.14-0.59] 0.001
- >3 AU/day
0.53 [0.17-1.65]
0.277 0.69 [0.18-2.60] 0.582
Female gender
0.25 [0.06-1.07] 0.062
Age at inclusion° - years
1.08 [1.05-1.11]
<10-3 1.07 [1.04-1.11] <10-3
Smoking>20 cig/day*
4.12 [2.22-7.64]
<10-3 3.88 [1.68-8.98] 0.002
CD4+ cell count>=200 cells/mm3* 0.48 [0.22-1.04]
0.062 0.34 [0.13-0.90] 0.030
Hyperlipidemia°
2.54 [1.33-4.85]
0.005 2.52 [1.10-5.75] 0.029
Undetectable viral load*
0.47 [0.27-0.81]
0.007
SD=standard deviation; AHR=adjusted hazard ratio ; CI=confidence interval
° Fixed variable (measured at M0 or M1)
Time-varying variable (the last available value before each visit)
CONCL US I ONS
Among the cART-treated patients followed-up in the French
APROCO-COPILOTE cohort:
Elevated alcohol consumption has no impact on CVD risk,
relative to abstainers category
However, moderate alcohol consumption seems to play a
protective role in the onset of CVD, after adjustment for
known risk factors
Due to the limited number and heterogeneity of CVD events,
a multi-cohort analysis may be needed to better explore the
impact of alcohol consumption on specific CVD in
ART-treated individuals